The metabolism and mechanism of action of the environmental carcinogens nitrosodiethanolamine, nitrosopyrrolidine, and nitrosomorpholine will be studied. Nitrosodiethanolamine occurs in the environment at higher levels than any other nitrosamine and nitrosopyrrolidine is also widely distributed; nitrosomorpholine can be formed readily by nitrosation in vivo. Metabolic profiles for these nitrosamines will be developed with special emphasis on the pathways of metabolic activation. The role of alpha-hydroxylation in activation of these compounds will be studied, using newly developed assays for alpha-hydroxylase activity. The relationship of alpha-hydoxylation to organ specificity and the inducibility of alpha-hydroxylase activity by environmental modifiers will be determined. The effects of environmental modifiers on carcinogenesis by these nitrosamines will be studied by bioassays in experimental animals. Other possible activation pathways such as beta-hydroxylation and oxidation will be investigated with the aid of the nitroasamine specific Thermal Energy Analyzer; bioassays of nitrosamine containing metabolites will be conducted. These experiments are expected to provide a clearer understanding of nitrosamine metabolism and mechanism of action, an important goal in view of the widespread occurrence and carcinogenicity of these compounds.